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Myth: "Gleason 6 never progresses"

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Posted 11/18/2017 6:26 PM (GMT -5)
I've had to address this misinformation so many times in my support groups and in here that I decided to put it all in one place.

The abridged version is:
• True GS6 never directly causes metastases. But knowing if it is a true GS6 is difficult.
• GS6 sometimes progresses to higher grades, sometimes doesn't.
• Eventually, it can progress to the point of causing metastases and death.
• There are some risk factors for progression, and some biomarkers, but we're still a long way off from distinguishing the GS6 that will progress from the GS6 that will never progress.
• The mechanism is unclear: common progenitor cell or accumulated genetic breakdown or both
• Active surveillance with periodic biopsies is necessary for early detection of any progression.

/pcnrv.blogspot.com/2017/11/myth-gleason-6-never-progresses.html
Posted 11/18/2017 7:49 PM (GMT -5)
The notion of "progression" is often misinterpreted, and is possibly misleading. Prostate cancer is largely understood to live as it was born (Journal of Cancer Research) rather than the cells themselves “progressing.”

An individual person’s case, however, “progresses” via findings in a follow-up biopsy if and when either (or both) of these two conditions transpire:
    a) the fertile “soil” from which the 3+3 (proper term for “Gleason 6”) “sprouts” (my term) some new higher Gleason cells, or
    b) some previously unidentified higher Gleason cells are found (which may or may not have been present when the previous biopsy was done).


Active Surveillance absolutely needs periodic follow-up biopsies to detect changes which may or may not warrant treatment. Most of the prime AS programs don't even consider you "in" the program until AFTER your 2nd confirmatory biopsy 6 or 12 months after the first...but after that 2nd biopsy, your risk of unfound higher grade cancers drops significantly.

Post Edited (NKinney) : 11/18/2017 6:16:29 PM (GMT-7)

Posted 11/18/2017 8:24 PM (GMT -5)
Boy am I confused now, I thought the direction of this forum was that Gleason 6 NEVER progressed, was extremely low risk and with all the high level imaging these days that confirm Gleason 6 it should never be treated. Somebody even wrote on here it was a crime to treat a Gleason 6 with surgery, what gives??
Posted 11/18/2017 8:31 PM (GMT -5)
Well...........................from what I can decipher..........................Never is not forever.
Posted 11/18/2017 8:37 PM (GMT -5)
TA or Others may be able to answer this..........but where does PCa come from and progress too?

I mean did my 4+3=7 miraculously appear as such or was it a 1+1=2 some years ago??
Posted 11/18/2017 8:56 PM (GMT -5)
mspt, three 5s,

Reread above. Your questions already answered.
Posted 11/18/2017 9:02 PM (GMT -5)
mspt, SOME have made that statement in the past. And, it has been published in medical journals that researchers (Epstein is one) have said that "TRUE G6 never progresses". The problem has always been (and still is) that there is no good way to identify by biopsy whether or not a discovered G6 is the 'good' kind or not.

And, for almost a 29 hand, THAT is the question, isn't it. How does it form, and where does it come from, and does it change in form? No clear answers.
Posted 11/18/2017 9:07 PM (GMT -5)
EXACTLY
Posted 11/18/2017 10:15 PM (GMT -5)
NKinney-
If you actually read the article, you will see that there is some controversy over what you consider to be "widely understood."

MSPT98-
That's why the article is there - to clear up your confusion. There is a lot of misinformation and misinterpretation in this forum, just as there is among doctors and elsewhere on the net. A lot of people state their beliefs with conviction that makes it sound convincing, but if there is no medical evidence, it is just another random opinion.

555J-
Read the section titled "How does GS6 progress to higher grades? What can we do about it?" If you go with the progenitor cell theory, the cancer is hatched at whatever grade it is. If you go with the genetic breakdown theory, there is slow continuous genetic degradation. Prostate cancer stem cells have been found sometimes, which argues for the progenitor cell theory. But they seem to be very rare, so it may be some combination of the two processes.

halbert-
As you will learn when you actually read that article, true GS6 certainly does progress in grade. It is slow, but it does sometimes happen. Models developed at Johns Hopkins estimated that of the 36% upgrading there, 12-24% was attributable to true grade progression, the rest to misclassification (sampling or misidentification).
Posted 11/18/2017 10:32 PM (GMT -5)
read the article?!?

foolish mortals...
Posted 11/18/2017 11:17 PM (GMT -5)
Do not know if my G6 has progressed to a higher grade, but it certainly has proved to be elusive in eradicating... :-(

pasayten
Posted 11/19/2017 4:52 AM (GMT -5)
Seems simple to me. I have cancer, I need to be monitored and for many treated. Whether the 6 signs of progress or the >6 appears there is not much difference in the plan, monitor and treat.

Clearly, something went wrong for cells to become cancerous. I am not sure the G6 will never theory. But that still does not change the plan, monitor, and treat when needed.
Denis
Posted 11/19/2017 8:07 AM (GMT -5)
Since all cancers are different you can't make a statement "this always does that" That's why they can't find a cure!
Posted 11/19/2017 8:37 AM (GMT -5)
TA,

Thanks for setting this straight!

For years I have read on this forum that a biopsy that comes up G6 can be interpreted as meaning you have an indolent cancer. Seems there may be more than one level of indolence (eg. Several variations of G6 cancer).

Come to think of it ..... weren’t G4 and G5’s considered cancererous at one time? Maybe G6a’s are cancerous and G6b’s are not ..... in other words as we get get smarter we can better classify what is and what is not a problem. Seems we have become a lot smarter over the last 10 years.

Seems a G4 or G5 could go to G6.

Post Edited (RCS) : 11/19/2017 6:52:59 AM (GMT-7)

Posted 11/19/2017 9:14 AM (GMT -5)
I know that when I was selected for AS at Johns Hopkins, they tested my PTEN level. My specialist at that time seemed to believe that gave them a better sense of confidence for my success in not having an upgrade.

It was similar when they were validating OncotypeDX, and tested me with that assay.

So, even with a G (3+3) there are several factors and tools to help guess if you can safely avoid treatment. That's the "active" part of AS.
Posted 11/19/2017 11:02 AM (GMT -5)

Tall Allen said...

halbert-
As you will learn when you actually read that article, true GS6 certainly does progress in grade. It is slow, but it does sometimes happen. Models developed at Johns Hopkins estimated that of the 36% upgrading there, 12-24% was attributable to true grade progression, the rest to misclassification (sampling or misidentification).

TA - I think that we had this discussion a year or two ago. I recall reading a quarterly publication from JH which said that they think that they had identified ONE case of a tumor genetically changing from G6 to a a higher grade. One out of about 1400 from their AS group. That makes the incidence of true progression very, very rare.

Am I mistaken in my comprehension? Where?

Thanks, as always.
Posted 11/19/2017 11:56 AM (GMT -5)
TA
Thanks for this illuminating analysis. I have been laboring under the view that my 4+5 was always just that as my JH surgeon told me after RP. In other words I had not progressed from a lower score.

In your opinion does this finding question the call for less screening due to over treatment of low risk men? If fewer men get screened doesn’t this risk some of them progressing to a potentially lethal grade by the time it’s discovered? Or are they saying that the damage from over treatment still outweighs the benefit from finding the very few cases that will have progressed to the point that it’s incurable?



Bob
Posted 11/19/2017 1:05 PM (GMT -5)
My initial scores were all GS 6 and my urologist did suggest I could monitor it. But I sought out a 2nd opinion from the University of Texas Medical Center in San Antonio. The doctor there scored one carcinoma as GS 7. Apparently there is a level of subjectivity in scoring. I didn't know at the time why I needed a 2nd opinion. I simply did it out of due diligence. That weighed on my decision.
Posted 11/19/2017 1:24 PM (GMT -5)
We are all aware that there are exceptions to every rule on PC. G6 grade migration seems to be an exception. 17,000 surgeries at JH on G6 patients showed no mets found on any. Klotz found that 1% of G6s were actually a variant that killed in three years regardless of treatment.
The real question is that does this change the current treatment for G6 which is either AS or some form of conventional treatment. I think not. The grade progression is rarely seen as are variants that look like a G6, and there are no current methods to readily identify these cases.
If it were shown that grade progression was common then the attractiveness of AS as a treatment option would greatly diminish. At this time I don't think that factoring in G6 grade progression into initial decision making would help any patients.
Posted 11/19/2017 1:27 PM (GMT -5)
Yeah, as I said, the initial choice of words can lead to misinterpretation or be misleading.

Case in point (there are several here to choose from):

Break60 said...
Or are they saying that the damage from over treatment still outweighs the benefit from finding the very few cases that will have progressed to the point that it’s incurable?

This statement seems to be a complete misuinderstanding of the basic fundamentals of Active Surveillance/Active Treatment for low risk cases. It’s the ol’ “throw ‘em under the bus” obfuscation. Let’s clarify this dangerous one:

Immediate, active treatment for men initially diagnosed with low-risk disease does not—repeating, DOES NOT—guarantee cure. There is a small percentage of these men who’s case progresses to BCR (see a) and b) from my previous post), metastasis, and eventual death. That’s right…death. Initially diagnosed with low-risk.

And gues what, there is also a small percentage of men with the SAME type of initially diagnosed low-risk disease who go initially onto AS, and their case progresses to BCR (see a) and b) from my previous post), metastasis, and eventual death. But guess what…those precentages are the same. Treatment or no treatment, the percentages are the SAME. What’s, therefore, the so-called “benefit” you speak of?

Words are important...

Post Edited (NKinney) : 11/19/2017 11:31:36 AM (GMT-7)

Posted 11/19/2017 1:31 PM (GMT -5)
The average male does not care about any of this...As far as he is concerned, the academics can go sit in the corner and argue about this forever. Should he be diagnosed with prostate cancer, he does not care about what grade it is. There is no debate. His urologist / surgeon tells him "We can cut this out, remove your cancerous prostate gland and you will be done with it, no worries"...Joe Sixpacks likely reply, "How soon can we get this done" and "How much is this going to cost ??" That's it, end of discussion...
Posted 11/19/2017 2:10 PM (GMT -5)
Wow! Something I sorta agree with Fairwind on. In another thread by Pratoman, I wrote:

NKinney said...

The "Anti-Cancer" book is very good.

In one of my favorite passages the author tells a revealing story about much about how people have their heads in the sand about diet, exercise, and other lifestyle modifications/integrative therapies. It starts by the author telling about some of the lifestyle modification programs:

    ...By participating in certain programs...patients try to take charge of their cancer, to learn to live in greater harmony with their bodies and their past, to seek peace of mind through yoga and meditation, to choose foods that fight cancer while avoiding those that promote its development. Their case histories show that they live two or three times longer than the average person with the same cancer at the same stage of development.

    An oncologist friend at the University of Pittsburgh, whom I told about these figures, objected: “These aren't ordinary patients. They're better educated, more motivated, and in better health. The fact that they live longer doesn't prove anything." But that is precisely the point: If patients are better informed about their disease, if they look after body and mind, and if they are given what they need to improve their health, then they can mobilize the body's vital functions to fight cancer. They live better and for longer.

I think that's what it's all about...live better and for longer.



Fairwind/Joe Sixpack doesn't care about studies and such...

Post Edited (NKinney) : 11/19/2017 12:41:40 PM (GMT-7)

Posted 11/19/2017 2:12 PM (GMT -5)
As Andrew implied, I can only imagine that several of you (JohnT and ASAdvocate) did not actually read the article, and simply imagine you know what is in it. I haven't seen any of your questions or comments that was not addressed in it. I can see that one source of misunderstanding is the difference between "grade progression," which is not rare (just slow), and the ability to cause metastases, which is almost unknown.

Grade progression occurs when a GS6 tumor becomes a GS7-10 tumor. The Gleason grade progresses to a higher grade. Metastases are tumors that have implanted in distant places, like lymph nodes, bones, and visceral organs. GS6 never directly causes metastases without progressing to a higher grade first. These are two different processes.

RCS- exactly so. Even high grade PIN may sometimes progress.

Break60- Grade progression from GS6 is very slow, so it doesn't matter much if a man with it is identified now or 8 years from now.
Posted 11/19/2017 3:32 PM (GMT -5)
So, two lessons:
1. "Always" and "Never" are rarely appropriate
2. Even with a low level G6 diagnosis (1-3 cores, low PSA), keeping an eye on it is mandatory
Posted 11/19/2017 4:28 PM (GMT -5)
And a third...no guarantees whether a G6 chooses AS or treatment,

A good question to ask oneself... would I rather treat now, while there is reason to believe that I'm a G6, or would I rather do AS and take the risk that by the time it becomes evident that I need treatment, I'm a g7(4+3).

Just to stir the pot ;-)...but IMO, a valid question, nevertheless.
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